Sphingolipids in neurodegenerative diseases

Front Neurosci. 2023 Feb 16:17:1137893. doi: 10.3389/fnins.2023.1137893. eCollection 2023.


Neurodegenerative Diseases (NDDs) are a group of disorders that cause progressive deficits of neuronal function. Recent evidence argues that sphingolipid metabolism is affected in a surprisingly broad set of NDDs. These include some lysosomal storage diseases (LSDs), hereditary sensory and autonomous neuropathy (HSAN), hereditary spastic paraplegia (HSP), infantile neuroaxonal dystrophy (INAD), Friedreich's ataxia (FRDA), as well as some forms of amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD). Many of these diseases have been modeled in Drosophila melanogaster and are associated with elevated levels of ceramides. Similar changes have also been reported in vertebrate cells and mouse models. Here, we summarize studies using fly models and/or patient samples which demonstrate the nature of the defects in sphingolipid metabolism, the organelles that are implicated, the cell types that are initially affected, and potential therapeutics for these diseases.

Keywords: Drosophila; Parkinson’s disease; ceramides; lysosome; mitochondria; neurodegeneration; sphingolipids.

Publication types

  • Review

Grants and funding

This work was supported by grants from the Huffington Foundation, the INADcure Foundation, the NIH (R24OD022005 and R24OD031447), and the Chair in Neurogenetics of the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital to HB, the Shan and Lee-Jun Wong fellowship from Baylor College of Medicine to DD. This work was also supported in part by the Baylor College of Medicine IDDRC (P50HD103555) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development for use of the Microscopy Core Facilities.